AAAS Gene

Alternative Names

  • AAAS
  • Aladin
  • Adracalin
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OMIM Number

605378

Gene Map Locus
12q13

Description

The AAAS gene gives instructions for the production of a protein named ALADIN whose role is not well recognized. ALADIN is found within cells in the nuclear envelope suggesting that its role lies in the movement of molecules into and out of the nucleus. It is also suggested that ALADIN plays a cell type specific function in regulating nucleocytoplasmic transport and that this role is significant for accurate maintenance and/or development of certain tissues.

Molecular Genetics

ALADIN consists of 546 amino acids and has a size of 59574 Da.

Epidemiology in the Arab World

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Other Reports

Algeria

Using linkage analysis in 12, mostly consanguineous, families with triple-A syndrome and originating from North Africa (five families from Algeria, and two families from Tunisia), Hadj-Rabia et al. (2000) confirmed that the disease locus maps to 12q13 (maximum lod score = 10.89 at marker D12S1604) and suggest that triple A is probably a genetically homogeneous disorder in patients of North African ancestry. Analysis of markers at 5 contiguous loci showed that most of the triple-A chromosomes were derived from a single founder chromosome, and Hadj-Rabia et al. (2000) speculated that the triple-A mutation was due to an ancient Arabian founder effect that occurred before migration to North Africa.

Using fine-mapping based on linkage disequilibrium in 10 North African inbred families (7 families with 10 affected individuals from Algeria, and 3 families with 5 affected individuals from Tunisia), Tullio-Pelet et al. (2000) identified a short ancestral haplotype on 12q13 (less than 1 cM), sequenced a BAC contig encompassing the triple-A minimal region, and identified a novel gene designated AAAS, encoding a 547-amino acid protein, called aladin, that was mutant in affected individuals. Nine of the 10 families from North African ancestry carrying allele 5 at the D12S1604 locus were found to have the same splice site mutation (IVS14+1G>A), and Tullio-Pelet et al. (2000) calculated that this founder mutation first occurred more than 2,400 years ago. The IVS14+1G>A mutation produced various abnormal transcripts, which resulted in premature translation termination upstream from exon 16. Two unrelated Tunisian patients from two of the families with the founder mutation had achalasia and alacrima without adrenal insufficiency, while each of their sibs had all three disease features. Tullio-Pelet et al. (2000) suggested that other unlinked genes or environmental factors may modify the expression of the mutant genotype. The remaining Algerian family was found to have nonsense mutation in exon 9 of the AAAS gene (1024C>T; R312X). The predicted product of AAAS, Aladin (for 'alacrima-achalasia-adrenal insufficiency neurologic disorder') belongs to the WD-repeat family of regulatory proteins, indicating a new disease mechanism involved in the triple-A syndrome. The expression of the gene in both neuroendocrine and cerebral structures pointed to a role in the normal development of the peripheral and central nervous systems.

Kuwait

Ismail et al. (2006) demonstrated the heterogeneous nature and the intra-familial phenotypic variability of Allgrove syndrome through sequencing the AAAS gene in a Palestinian family consisting of the parents, three healthy children, and an affected boy and a girl aged 12 and 19 years old. A novel homozygous mutation within intron 5 (IVS5 + 1G-A) was identified in both siblings while a heterozygous mutation was found in both parents and their three children N.B.: Classification not applicable to gene loci.

Palestine

[See: Kuwait > Ismail et al., 2006].

Tunisia

[See: Algeria > Hadj-Rabia et al., 2000; Tullio-Pelet et al., 2000].

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